Clinical and pathological analyses of gastric-type cervical adenocarcinoma and its prognostic relevance.

Background: Gastric-type endocervical adenocarcinoma (GAS), the predominant non-human papillomavirus cervical cancer, is highly aggressive with poor prognosis. No drugs are effective against advanced or recurrent GAS.

Objective: This study aimed to analyze the clinical and pathological characteristics of GAS, evaluate the expression of targets for targeted drug therapy, and assess the predictive value of Immunoscore for prognosis.

Design: The study retrospectively analyzed the clinical and pathological characteristics and follow-up data of 107 cases of GAS and 523 of human papillomavirus-associated cervical adenocarcinoma (HPVA) treated surgically at Zhejiang Cancer Hospital between January 2015 and December 2022.

Methods: Immunohistochemistry was used to detect the expressions of Tumor Protein 53 (P53), p16 protein (P16), Human Epidermal Growth Factor Receptor 2, Mucin 6, Programmed Death-Ligand 1 (PD-L1), Claudin 18.2, and immune markers Cluster of Differentiation 3/Cluster of Differentiation 8 in tumors. Ridge regression analysis was employed to obtain an Immunoscore, and receiver-operating characteristic curves were used to calculate the cutoff value to divide the Immunoscores into the low-risk and high-risk groups. The Kaplan-Meier method and Cox proportional hazards regression model were used in the survival and multivariate analyses, respectively.

Results: Compared with HPVA, GAS was associated with later staging, larger tumor size, deeper invasion, and higher risks of lymph node metastasis, lymphovascular space invasion, parametrial involvement, ovarian metastasis, and peritoneal metastasis ( < 0.05). For patients in stages IA-IIIC2, the risk of recurrence/metastasis in GAS was significantly higher than that in HPVA (43.9% vs 21.2%,  < 0.001). The 5-year rates of progression-free survival (PFS; 44% vs 75.4%,  < 0.001) and overall survival (OS; 47.9% vs 82.5%,  < 0.001) were significantly lower in GAS than in HPVA. In the multivariate analysis, the histological type of GAS was an independent risk factor for OS (hazard ratio (HR) = 1.773,  = 0.023). In GAS, 71.7% and 46.7% were positive for Claudin 18.2 and PD-L1 (combined proportion score ⩾1), respectively. Four (3.7%) patients showed 3+ expression of Her-2. Cox multivariate analysis results indicated the Immunoscore as an independent predictive factor for PFS (HR = 2.532,  = 0.002) and OS (HR = 3.147,  = 0.003) in patients with GAS. The 5-year OS rates for the low- and high-risk groups based on the Immunoscore were 62.1% and 0% ( < 0.001), and the 5-year PFS rates were 57.3% and 9.0% ( < 0.001), respectively.

Conclusion: GAS is extremely aggressive and prone to recurrence and has a poor prognosis. The Immunoscore is an independent prognostic factor of GAS. Claudin 18.2 is expressed at high rates in GAS and is a potential therapeutic target.